Antimicrobial Prophylaxis in Patients Who Underwent a Transurethral Resection of Bladder (TURB)

NCT04209192 | Completed Phase 2 DMC

• 1 other identifier: URO-2995-19-20-1
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Antimicrobial prophylaxis in urological procedures is aimed to reduce the risk of local and systemic postoperative infections such as urinary tract infection or surgical site infection. It should be recommended only when the potential benefit exceeds the anticipated risks and costs. However, a wide variation in the use of periprocedural prophylactic antibiotics has been demonstrated, which frequently is incurred as an inappropriate selection of antimicrobials, inadequate schedule of administration or excessive duration of prophylaxis. The increase in multidrug resistance of antibiotics in recent decades has been associated with its misuse, resulting in an increased rate of morbidity and mortality, prolonged hospital stays and increased care costs. Specifically, resistance to fluoroquinolones has increased its prevalence, a group of antibiotics widely used in urology. Therefore, local resistance patterns should be considered before following recommendations, especially in populations with poor control of antimicrobial use. Transurethral resection of bladder (TURB) has become a frequent surgical procedure, as it is the main diagnostic and therapeutic tool for bladder cancer, representing the ninth most common malignancy in the world. However, no recent randomized clinical trial has investigated antimicrobial prophylaxis for TURB. It is well known that an expected complication of TURB is urinary tract infection (UTI), which is the most common healthcare related infection worldwide. Under this premise, a randomized clinical trial is proposed to analyze the current panorama of UTI as a transcendent postoperative complication of TURB, under the context of the new emerging resistance parameters. The use of fosfomycin trometamol is proposed as a good potential option for urological procedures due to its high activity against multidrug-resistant gram-negative bacteria and its favorable pharmacokinetic parameters that guarantees wide tissue penetration and a high urinary concentration, in a single dose, the which will be compared with the control group with traditional prophylaxis (amikacin). The relative risk of UTI will be estimated, as well as the attributable risk of the main risk factors associated with this infection, allowing a better characterization of this population for adequate decision making regarding this clinical challenge.

Conditions

Urinary Tract Infections; Bladder Cancer; Urologic Surgical Procedures

Keywords

UTI; Prophylaxis; Urinary Tract Infections; TURB; Fosfomycin; Amikacin; Transurethral Resection of Bladder

Outcome Measures

Primary Outcomes (4)

• Incidence of urinary tract infection after transurethral resection of bladder

  Measurement tool: Clinical manifestations of urinary tract infection plus positive urine culture. Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A positive urine culture will be confirmed using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL Clinical manifestations of urinary tract infection: Patient presenting 1 or more of the following signs or symptoms: fever, dysuria, frequency, hematuria, lumbar pain, costovertebral angle tenderness)

  30 days after procedure

• Incidence of asymptomatic bacteriuria after transurethral resection of bladder

  Measurement tool: Positive urine culture and no clinical manifestation of urinary tract infection Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A urine culture will be positive using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL No clinical manifestations of urinary tract infection

  30 days after procedure

• Relative risk of asymptomatic bacteriuria after transurethral resection of bladder

  Measurement tool: Positive urine culture and no clinical manifestation of urinary tract infection Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A urine culture will be positive using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL No clinical manifestations of urinary tract infection

  30 days after procedure

• Relative Risk of urinary tract infection after transurethral resection of bladder

  Measurement tool: Clinical manifestations of urinary tract infection plus positive urine culture. Measurement unit: Colony-forming unit (CFU) per milliliter (mL) depending on how the urine sample was took. A positive urine culture will be confirmed using the next parameters: For midstream urine a count greater or equal to 100,000 CFU/mL and for urine obtained from a urethral catheter a count a count greater or equal to 100 CFU/mL Clinical manifestations of urinary tract infection: Patient presenting 1 or more of the following signs or symptoms: fever, dysuria, frequency, hematuria, lumbar pain, costovertebral angle tenderness)

  30 days after procedure

Secondary Outcomes (24)

• Relative risk of patients presenting a single bladder tumor

  During procedure

• % of patients presenting a single bladder tumor

  During procedure

• Relative risk of patients presenting 2 to 7 bladder tumors

  During procedure

• % of patients presenting 2 to 7 bladder tumors

  During procedure

• Relative risk of patients presenting more than 7 bladder tumors

  During procedure

Other Outcomes (23)

• Relative risk of positive nitrites in preoperative urinalysis

  30 days before procedure

• Relative risk of positive leukocytes in urine in preoperative urinalysis

  30 days before procedure

• Relative risk of positive erythrocytes in urine in preoperative urinalysis

  30 days before procedure

Study Arms (2)

Control group (Amikacin)

ACTIVE COMPARATOR

Patients in the control group will receive amikacin as prophylactic antibiotic. It will be administered intravenously 30 minutes before procedure. Patients with an estimated glomerular filtration rate (EGFR) greater or equal than 70 ml/min will receive 1 gram of Amikacin. Patients with an EGFR less than 70 ml/min will received a calculated dose following the next parameters. Patients with EGFR between 69-40 ml/min should receive: the calculated GFR x 0.18 = mg/kg. Patients with EGFR less than 40 ml/min should receive: the calculated GFR x 0.36 = mg/kg.

Drug: Amikacin

Intervention group (Fosfomycin)

EXPERIMENTAL

Patients in the intervention group will receive Fosfomycin trometamol as prophylactic antibiotic. It will be administered orally in the night before procedure. Patients must be on fasting and will receive 3 grams.

Drug: Fosfomycin Tromethamine 3G Sachet

Interventions

Fosfomycin Tromethamine 3G Sachet DRUG

Is the prophylactic drug which will be used in the intervention group.

Also known as: Fosfomycin

Intervention group (Fosfomycin)

Amikacin DRUG

Is the prophylactic drug which will be used in the control group.

Also known as: Control

Control group (Amikacin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years old of age
• Patients with a programmed TURB
• Absence of urinary tract infection (negative urine culture and no clinical manifestations for urinary tract infection)

You may not qualify if:

• Patients with asymptomatic bacteriuria
• Patients with positive urine culture before procedure
• Patients with urinary catheterization

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead
• Laboratorios Senosiain, S.A. de C.V.: collaborator

Study Sites (1)

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, 14080, Mexico

Location

Related Publications (28)

• Herr HW, Donat SM, Reuter VE. Management of low grade papillary bladder tumors. J Urol. 2007 Oct;178(4 Pt 1):1201-5; discussion 1205. doi: 10.1016/j.juro.2007.05.148. Epub 2007 Aug 14.

  PMID: 17698090 BACKGROUND

• Holzbeierlein JM, Smith JA Jr. Surgical management of noninvasive bladder cancer (stages Ta/T1/CIS). Urol Clin North Am. 2000 Feb;27(1):15-24, vii-viii. doi: 10.1016/s0094-0143(05)70230-5.

  PMID: 10696241 BACKGROUND

• Mayorga, G; Ibarra, O; Sedano, B; Trujillo, O; Cornejo, D; Palmeros, R;…Pacheco, G. (2014) Aplicación de nomogramas en México para cáncer de vejiga en pacientes del Hospital General "Dr Manuel Gea González". Revista Mexicana de Urología, 74(1),3-8. https://doi.org/10.1016/s2007-4085(15)30002-1

  BACKGROUND

• Parkin DM. The global burden of urinary bladder cancer. Scand J Urol Nephrol Suppl. 2008 Sep;(218):12-20. doi: 10.1080/03008880802285032.

  PMID: 19054893 BACKGROUND

• Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.

  PMID: 21351269 BACKGROUND

• Sedano-Basilio, J; Mayorga-Gómez, E; Garza-Sainz, G; Conrejo-Dávila, V; Uberetagoyena-Tello de Meneses, I; Palmeros-Rodríguez, A;… Pacheco-Gahbler, C. (2016) Epidemiología de los tumores genitourinarios en una década. Revista Mexicana de Urología, 76(3), 131-140. https://doi.org/10.1016/j.uromx.2016.01.004

  BACKGROUND

• Pycha, A. & Palermo, S. (2005) Transurethral Resection of Bladder Tumors. In R. Hoenfellner & J. Stolzenburg (Eds.) Manual Endourology (pp. 55-70) Berlín: Springer

  BACKGROUND

• Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, Nicolle LE; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar 1;50(5):625-63. doi: 10.1086/650482.

  PMID: 20175247 BACKGROUND

• Junuzovic D, Hasanbegovic M, Zvizdic S, Hamzic S, Zunic L. The connection between endourological procedures and occurrence of urinary infections. Mater Sociomed. 2014 Aug;26(4):237-41. doi: 10.5455/msm.2014.237-241. Epub 2014 Aug 26.

  PMID: 25395884 BACKGROUND

• Alsaywid BS, Smith GH. Antibiotic prophylaxis for transurethral urological surgeries: Systematic review. Urol Ann. 2013 Apr;5(2):61-74. doi: 10.4103/0974-7796.109993.

  PMID: 23798859 BACKGROUND

• Matulewicz RS, Sharma V, McGuire BB, Oberlin DT, Perry KT, Nadler RB. The effect of surgical duration of transurethral resection of bladder tumors on postoperative complications: An analysis of ACS NSQIP data. Urol Oncol. 2015 Aug;33(8):338.e19-24. doi: 10.1016/j.urolonc.2015.05.011. Epub 2015 Jun 10.

  PMID: 26072111 BACKGROUND

• Rolston K.V. (2003) Pseudomonas Aeruginosa Infections in Cancer Patients. In: Hauser A.R., Rello J. (eds) Severe Infections Caused by Pseudomonas Aeruginosa. Perspectives on Critical Care Infectious Diseases, vol 7. Springer, Boston, MA

  BACKGROUND

• Mazzei T, Diacciati S. Pharmacological aspects of the antibiotics used for urological diagnostic procedures. J Chemother. 2014 Oct;26 Suppl 1:S24-34. doi: 10.1179/1120009X14Z.000000000234.

  PMID: 25245708 BACKGROUND

• Wolf JS Jr, Bennett CJ, Dmochowski RR, Hollenbeck BK, Pearle MS, Schaeffer AJ; Urologic Surgery Antimicrobial Prophylaxis Best Practice Policy Panel. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008 Apr;179(4):1379-90. doi: 10.1016/j.juro.2008.01.068. Epub 2008 Feb 20.

  PMID: 18280509 BACKGROUND

• Yamamoto S, Shigemura K, Kiyota H, Wada K, Hayami H, Yasuda M, Takahashi S, Ishikawa K, Hamasuna R, Arakawa S, Matsumoto T; Japanese Research Group for UTI. Essential Japanese guidelines for the prevention of perioperative infections in the urological field: 2015 edition. Int J Urol. 2016 Oct;23(10):814-824. doi: 10.1111/iju.13161. Epub 2016 Aug 16.

  PMID: 27531443 BACKGROUND

• Mrkobrada M, Ying I, Mokrycke S, Dresser G, Elsayed S, Bathini V, Boyce E, Luke P. CUA Guidelines on antibiotic prophylaxis for urologic procedures. Can Urol Assoc J. 2015 Jan-Feb;9(1-2):13-22. doi: 10.5489/cuaj.2382. No abstract available.

  PMID: 25737749 BACKGROUND

• Yokoyama M, Fujii Y, Yoshida S, Saito K, Koga F, Masuda H, Kobayashi T, Kawakami S, Kihara K. Discarding antimicrobial prophylaxis for transurethral resection of bladder tumor: a feasibility study. Int J Urol. 2009 Jan;16(1):61-3. doi: 10.1111/j.1442-2042.2008.02188.x.

  PMID: 19120528 BACKGROUND

• Sotomayor-de Zavaleta, M; Ponce de León-Garduño, A; Guzmán-Esquivel, J. & Rosas-Nava, E. (2015). Recomendaciones de expertos mexicanos en en tratamiento de las infecciones del tracto urinario en pacientes adultos, embarazadas y niños. Revista Mexicana de Urología, 72 (2), 1-46

  BACKGROUND

• Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009 Jan 1;48(1):1-12. doi: 10.1086/595011.

  PMID: 19035777 BACKGROUND

• Panach-Navarrete J, Valls-Gonzalez L, Sanchez-Cano E, Medina-Gonzalez M, Castello-Porcar A, Martinez-Jabaloyas JM. Comparison of three different antibiotic protocols in transurethral resection of bladder tumour and the possible infectious risk factors: A non-randomized, prospective study. Can Urol Assoc J. 2018 Nov;12(11):E466-E674. doi: 10.5489/cuaj.5207. Epub 2018 Jun 8.

  PMID: 29989880 BACKGROUND

• Junuzovic, D; Hasanbegovic, M. & Kovacevic-Prstojevic, J (2011) The Incidence of Acquired Urinary Tract Infections in patients After Transurethral Resection of Bladder Tumors. MSM, 23 (2): 91-92

  BACKGROUND

• Herwaldt LA, Cullen JJ, Scholz D, French P, Zimmerman MB, Pfaller MA, Wenzel RP, Perl TM. A prospective study of outcomes, healthcare resource utilization, and costs associated with postoperative nosocomial infections. Infect Control Hosp Epidemiol. 2006 Dec;27(12):1291-8. doi: 10.1086/509827. Epub 2006 Nov 17.

  PMID: 17152025 BACKGROUND

• Andriole VT. The quinolones: past, present, and future. Clin Infect Dis. 2005 Jul 15;41 Suppl 2:S113-9. doi: 10.1086/428051.

  PMID: 15942877 BACKGROUND

• Delavierre D, Huiban B, Fournier G, Le Gall G, Tande D, Mangin P. [The value of antibiotic prophylaxis in transurethral resection of bladder tumors. Apropos of 61 cases]. Prog Urol. 1993 Aug-Sep;3(4):577-82. French.

  PMID: 8401618 BACKGROUND

• Upton JD, Das S. Prophylactic antibiotics in transurethral resection of bladder tumors: are they necessary? Urology. 1986 May;27(5):421-3. doi: 10.1016/0090-4295(86)90406-1.

  PMID: 3518183 BACKGROUND

• MacDermott JP, Ewing RE, Somerville JF, Gray BK. Cephradine prophylaxis in transurethral procedures for carcinoma of the bladder. Br J Urol. 1988 Aug;62(2):136-9. doi: 10.1111/j.1464-410x.1988.tb04292.x.

  PMID: 3044484 BACKGROUND

• Ishizaka K, Kobayashi S, Machida T, Yoshida K. Randomized prospective comparison of fosfomycin and cefotiam for prevention of postoperative infection following urological surgery. J Infect Chemother. 2007 Oct;13(5):324-31. doi: 10.1007/s10156-007-0544-5. Epub 2007 Oct 30.

  PMID: 17982722 BACKGROUND

• Patel SS, Balfour JA, Bryson HM. Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections. Drugs. 1997 Apr;53(4):637-56. doi: 10.2165/00003495-199753040-00007.

  PMID: 9098664 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections; Urinary Bladder Neoplasms

Interventions

Fosfomycin; Amikacin

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Urinary Bladder Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Ricardo A Castillejos, MD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Urology Attending

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: December 24, 2019
• Study Start: January 1, 2020
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: April 4, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)